Digital Commons Network^™

The Medial Olivocochlear Efferent Pathway Potentiates Cochlear Amplification In Response To Hearing Loss, Ariadna Cobo-Cuan, Marcela A Morán, Bong Jik Kim, Clayton B Walker, Michael J Serafino, Frank Macias-Escriva, Juemei Wang, James B Dewey, Brian E Applegate, Matthew J Mcginley, John S Oghalai

Faculty, Staff and Students Publications

The mammalian cochlea receives efferent feedback from the brain. Many functions for this feedback have been hypothesized, including on short timescales, such as mediating attentional states, and long timescales, such as buffering acoustic trauma. Testing these hypotheses has been impeded by an inability to make direct measurements of efferent effects in awake animals. Here, we assessed the role of the medial olivocochlear (MOC) efferent nerve fibers on cochlear amplification by measuring organ of Corti vibratory responses to sound in both sexes of awake and anesthetized mice. We studied long-term effects by genetically ablating the efferents and/or afferents. Cochlear amplification increased …

Mitochondrial Responses To Conventional And Ultra-High Dose Rate (Flash) Radiation, Kevin Liu, Henry Gatica-Gutierrez, Sofía Vargas-Hernández, Nefetiti Mims, Ariana Acevedo-Diaz, Brett Velasquez, Denae Neil, Edgardo Aguilar, Matthew D Meyer, Gloria V Echeverria, Albert C Koong, Michael T Spiotto, Anna-Karin Gustavsson, Emil Schüler

Faculty, Staff and Students Publications

Purpose: Ultra-high dose rate (>40 Gy/s, FLASH) radiation therapy (RT) provides equivalent tumor control while reducing normal tissue toxicity relative to conventional dose rate (CONV) RT. However, the mechanisms underlying the observed FLASH effect are unknown. We hypothesized that the preservation of mitochondrial integrity in nontumorigenic cells by FLASH RT could be a key factor in reducing normal tissue toxicity and improving overall treatment outcomes.

Methods: We examined mitochondrial health and function after CONV and FLASH in vitro, ex vivo, and in vivo through assays of metabolic flux, mitochondrial membrane potential, mitochondrial reactive oxygen species (ROS), mitochondrial DNA damage …

An Unsupervised Map Of Excitatory Neuron Dendritic Morphology In The Mouse Visual Cortex, Timo Lüddecke, Brendan Celii, Paul G Fahey, Eric Y Wang, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Forrest Collman, Nuno Maçarico Da Costa, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, R Clay Reid, Casey M Schneider-Mizell, H Sebastian Seung, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Wenjing Yin, Szi-Chieh Yu, Jacob Reimer, Philipp Berens, Andreas S Tolias, Alexander S Ecker

Faculty, Staff and Students Publications

Neurons in the neocortex exhibit astonishing morphological diversity, which is critical for properly wiring neural circuits and giving neurons their functional properties. However, the organizational principles underlying this morphological diversity remain an open question. Here, we took a data-driven approach using graph-based machine learning methods to obtain a low-dimensional morphological "bar code" describing more than 30,000 excitatory neurons in mouse visual areas V1, AL, and RL that were reconstructed from the millimeter scale MICrONS serial-section electron microscopy volume. Contrary to previous classifications into discrete morphological types (m-types), our data-driven approach suggests that the morphological landscape of cortical excitatory neurons is …

Gramd1b Is A Regulator Of Lipid Homeostasis, Autophagic Flux And Phosphorylated Tau, Diana Acosta Ingram, Jacob Marsh, Celeste M Karch, Et Al.

2020-Current year OA Pubs

Lipid dyshomeostasis and tau pathology are present in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). However, the relationship between lipid dyshomeostasis and tau pathology remains unclear. We report that GRAM Domain Containing 1B (GRAMD1B), a nonvesicular cholesterol transporter, is increased in excitatory neurons of human neural organoids (HNOs) with the MAPT R406W mutation. Human FTLD, AD cases, and PS19 tau mice also have increased GRAMD1B expression. We show that overexpression of GRAMD1B increases levels of free cholesterol, lipid droplets, and impairs autophagy flux. Modulating GRAMD1B in iPSC-derived neurons also alters key autophagy-related components such as PI3K, phospho-AKT, and p62, …

Activation Of Endoplasmic Reticulum-Localized Metabotropic Glutamate Receptor 5 (Mglu5) Triggers Calcium Release Distinct From Cell Surface Counterparts In Striatal Neurons, Yuh-Jiin I Jong, Steven K Harmon, Karen L O'Malley

2020-Current year OA Pubs

Metabotropic glutamate receptor 5 (mGlu

An In Vivo Microscopy Dataset For The Characterization Of Leukocyte Death, Alain Pulfer, Diego Ulisse Pizzagalli, Miguel Palomino Segura, Nina Germic, Tommaso Virgilio, Pau Carrillo Barbera, Paola Antonello, Marcus Thelen, Hans-Uwe Simon, Rolf Krause, Santiago F Gonzalez

Faculty, Staff and Student Publications

Recent advancements in intravital microscopy have enabled the study of cell death in vivo under various experimental conditions, such as infection and cancer. However, the limited throughput of this technology, together with a lack of openly accessible datasets, affects the development of algorithms for the automatic detection and characterization of cell death, which in turn require the integration of extensive and curated datasets. To address these needs, we present a curated dataset of microscopy videos depicting the death of neutrophils, eosinophils, and dendritic cells, acquired in the spleen and in the lymph node of mice under inflammatory conditions. The dataset …

Cell Type-Specific Multi-Omics Analysis Of Cocaine Use Disorder In The Human Caudate Nucleus, Laura Stertz, Fabian Streit, Diana Avetyan, Maja P Völker, Svenja Müller, Anita C Hansson, Thomas D Meyer, Marcella Rietschel, Julia Ladewig, Rainer Spanagel, Ana M M Oliveira, Consuelo Walss-Bass, Rick E Bernardi, Philipp Koch, Stephanie H Witt

Faculty, Staff and Student Publications

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 30,030 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells. We observed 1485 differentially regulated genes and 10,342 differentially accessible peaks, with alterations in MSNs and astrocytes related to neurotransmitter activity and synapse organization. Gene regulatory network analysis identified transcription factors including ZEB1 as exhibiting distinct CocUD-specific subclusters, …

Bioseq: A Molecular Intelligence Platform Based On Organism-On-Chip Technology For Bridging Data Gaps Between C. Elegans And Humans, Hunter Edwards, Adnan Qureshi, Mizanur Rahman, Tyler Chiriboga, Amar Chittiboyina, Ikhlas Khan, Siva Vanapalli

Oxford ICSB

The FDA Modernization Act 2.0, emphasizes the urgent need for New Approach Methodologies (NAMs) to replace conventional animal testing in safety and efficacy assessments. NemaLife’s organism-on-chip platform, utilizing C. elegans, microfluidics and visual AI, provides a high throughput platform for in vivo screening. To enhance human relevance and reduce the inter-species gap between C. elegans and human, we developed BioSeq, a novel discovery workflow, based on high-throughput transcriptomics. Leveraging the 60-80% homology between C. elegans and human genomes, BioSeq translates worm gene expression data to human orthologs. This enables: (i) identification of differentially expressed human-relevant genes triggered by bioactive ingredients …

Current Regulatory And Enforcement Landscape Under Mocra, Diane Mcenroe

Oxford ICSB

The Modernization of Cosmetics Regulation Act of 2022 (MoCRA) became effective December 29th, 2023 and is the most significant expansion of FDA’s authority to regulate cosmetics since the FD&C Act was enacted in 1938. MoCRA expands the FDA's authority over cosmetics and creates new compliance obligations for manufacturers. Diane McEnroe, an FDA regulatory lawyer at Sidley Austin, LLP, will provide an overview of the law and its implication for cosmetic manufacturers and marketers. The presentation will also provide an update on the current regulatory and enforcement landscape to date, including considerations about follow on litigation when there has been publicity …

Herbal Medicine For The Management Of Asthma In Taiwan: Insights From Big Data, Laboratory Studies, And Clinical Research, Hung-Rong Yen, Chuan-Teng Liu, Ying-Chyi Song

Oxford ICSB

Introduction: Asthma affects individuals across all age groups and poses a significant public health challenge in Taiwan, with high morbidity rates and substantial healthcare burdens. Traditional medicine theory emphasizes restoring the yin-yang balance, achieved through methods such as herbal medicine. Real-world data from Taiwan highlight the growing reliance on complementary therapies due to recurrent exacerbations and the potential side effects of conventional asthma medications. Materials and Methods: First, we analyzed the National Health Insurance Research Database, encompassing a population of 23 million in Taiwan, to identify the most commonly prescribed Chinese herbal medicines. Subsequently, we conducted in vitro experiments and …

Intoxicating Cannabinoids And Impurities In Hemp-Derived Products In Us Markets, Mahmoud Elsohly

Oxford ICSB

This talk will examine the nature and source of a number of intoxicating cannabinoids and impurities, widely available in the US and marketed as “hemp-derived” and thus promoted as legal and safe products. The presentation will elaborate on the 2018 Farm Bill, the definition of Hemp and the consequences of the interpretation of the definition on the composition of products on the market. Of particular emphasis will be the prevalence of Delta-8 THC in these products and the incorporation of their intoxicating cannabinoids.

A Randomized, Double-Blinded, Parallel, Placebo-Controlled Clinical Trial To Study The Effect And Safety Of Korean Red Ginseng Extract Powder On Cardiovascular Health Markers In Healthy Adults, Amir Rafie

Oxford ICSB

Cardiovascular disease is a prevalent condition that imposes a significant socioeconomic burden. Korean red ginseng, a medicinal plant traditionally used in Asia, has been suggested to potentially protect against cardiovascular dysfunction by improving blood flow. We conducted a randomized, double-blind, parallel, placebo-controlled trial to assess the effects of Korean Red Ginseng Extract Powder (G1899) on blood flow and platelet aggregation (primary endpoints) and other cardiovascular health markers (e.g., blood coagulation parameters) in healthy adults. Participants (N=108) were randomized in a 1:1:1 ratio to three groups: high dose (2000 mg G1899 per day), low dose (480 mg G1899 per day), and …

Ashwagandha – Is It Safe? A Toxicologist’S Perspective, Mukesh Summan

Oxford ICSB

Withania somnifera (WS) also known as ashwagandha is a herb commonly used in Ayurvedic medicine with recorded use dating back centuries. Different plant parts including roots, leaves, fruits, seeds and stems are purported to have various biological actions such as anti-inflammatory, anti-diabetic, anti-stress, anti-anxiety when used alone or in combination with other plants. Despite this long history of use as a traditional herb in Indian medicine and world-wide as a food supplement, regulatory health authorities have begun to question the safety of WS due clinical cases of herb-induced liver injury from products labelled as containing ashwagandha and concerns for WS …

Evaluation Of Potential Hormonal Activities Of Ashwagandha (Withania Somnifera), Guenter Vollmer

Oxford ICSB

No abstract provided.

Ashwagandha: Is It Safe? A Review Of The Clinical Evidence., Thomas Brendler, Elizabeth Williamson

Oxford ICSB

Over the last decade, ashwagandha (Withania somnifera (L.) Dunal, AS) has been brought under increasing scrutiny regarding its safety for the use in food supplements, culminating in a recent recommendation for an Article 8 procedure according to Regulation (EC) No 1925/2006 in the European Union (EU). Once executed, this could lead to a ban of the use as an ingredient in food supplements. One of the regulators’ concerns is the purported lack of clinical safety data combined with evidence for what may constitute a safe daily dose. In this overwiew we assess evidence stemming from 96 clinical trials conducted over …

The Role Of Animals In Pediatric Occupational Therapy Telehealth Interventions: A Survey Of Therapist Perspectives., Macy Burr, Catherine Le

Occupational Therapy Collection

AIMS: Animal-assisted interventions (AAI) incorporate animals in health, education, or human services to improve participant health and well-being. AAI can decrease stress, increase happiness, and improve motor skills. During the COVID-19 pandemic, virtual AAI programs became more common. Telehealth also became more prevalent in occupational therapy. This study explored the perceptions of occupational therapy (OT) practitioners regarding including animals in telehealth OT pediatric interventions.

METHODS: Survey responses were collected from 18 occupational therapists who have included animals in OT pediatric telehealth interventions.

RESULTS: Most participants agreed that incorporating animals into telehealth enhanced the therapeutic experience for their clients, as they …

Protecting Global Health Partnerships In The Era Of Destructive Nationalism, Maya Adam, Desiree Labeaud, Nokwanele Mbewu, Jennifer Gates, Randall Waechter, Mercy Borbor-Cordova, Lydiah Kibe, Sonia Alvarez, Annie Dori, Anil Bilimale, Meggie Mwoka, Jessica Deffler, Michele Spring, Avriel Diaz, Rachael Farquhar, Willy Dunbar, Comfort Phiri, Valerie Luzadis, Nicole Redvers, Cristina Alonso, Rosemary Rochford, Rachel Lowe, Kareem Coomansingh, Moses Laman, Rebeca Sultana, Sadie Ryan, Amaya Bustinduy, Anita Hargrave-Bouagnon, Shazia Ruybal-Pesántez, Zebedee Kerry, Trevor Kelebi, Samuel Mcewen, Leanne Robinson, Maritza Salazar Campo, Till Bärnighausen

Department of Family & Community Medicine Faculty Papers

No abstract provided.

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Tumor-Derived Arachidonic Acid Reprograms Neutrophils To Promote Immune Suppression And Therapy Resistance In Triple-Negative Breast Cancer, Fengshuo Liu, Zhan Xu, Xiaoxin Hao, Ling Wu, Weijie Zhang, Hilda L Chan, Bo Wei, Philip L Lorenzi, Yang Gao, Igor Bado, Luis Becerra-Dominguez, Charlotte Helena Rivas, Sergio Aguirre, Bradley C Pingel, Yi-Hsuan Wu, Yunfeng Ding, Jun Liu, David G Edwards, Livia S Eberlin, Xiang H-F Zhang

Faculty, Staff and Students Publications

The combination of immune checkpoint blockade and chemotherapies is the standard of care for triple-negative breast cancer (TNBC). However, initially, responsive tumors can still develop recurrences, suggesting acquired resistance mechanisms that remain poorly understood. Herein, we discover that TNBC cells surviving anti-programmed cell death protein-1 (anti-PD-1) and chemotherapy treatment accumulate neutral lipids. Disrupting lipid droplet formation in cancer cells reverses resistance and mitigates the immunosuppressive microenvironment. Single-cell RNA sequencing reveals a subset of neutrophils exhibiting a lipid-laden phenotype similar to adjacent tumor cells. Mechanistically, tumor-derived extracellular vesicles carrying lipids, including arachidonic acid (AA), mediate neutrophil reprogramming. Blocking dietary intake of …

The Cardiovascular Care Of The Pediatric Athlete, Jonathan B Edelson, Susan Etheridge, Dermot M Phelan, Keri Shafer, Chris Snyder, Silvana Molossi, Alfred Danielian, Eli M Friedman, Jeff Hsu, Mustafa Husaini, Eugene H Chung, Matthew W Martinez, Aaron L Baggish, Benjamin D Levine, Jonathan H Kim, American College Of Cardiology Sports & Exercise Cardiology Council

Faculty, Staff and Students Publications

Sports cardiology broadly encompasses the cardiovascular care of individuals who place a high premium on habitual exercise, sports performance, and/or sports competition. Some of the essential aspects within sports cardiology include the preparticipation cardiac evaluation and the management of cardiac diseases in athletes. Although most sports cardiology practitioners are trained in adult cardiology, a significant number of individuals who participate in sports are pediatric-aged, < 18 years old. Up to two-thirds of children in middle and high school participate in organized sports or are involved in nonorganized recreational sports. The cardiovascular care of pediatric-aged athletes can be challenging because many of the classic tenets and principles in adult sports cardiology do not fully generalize to pediatrics, and there is a lack of the evidence base that may be present for adult athletes. The epidemiology, presentation, and progression of cardiovascular diseases can be significantly different between pediatric and adult athletes. The evaluation of potential diseases and management considerations may also differ between pediatric and adult athletes. Similar to adults, there are "gray zones" where it is difficult to differentiate between normal exercise-induced cardiac remodeling and true cardiac pathology, but the additional lack of normative standards further complicates assessments in pediatric athletes. Management decisions for pediatric athletes are generally based on limited data but carry substantial short- and long-term implications. Thus, shared decision-making as part of the determination of clinical management strategies and for sports participation is critical and requires the participation of the parents or guardian(s). In this state-of-the-art review, key differences between pediatric and adult-aged athletes are highlighted. Specifically, how to define the "pediatric athlete," consider cardiovascular adaptations observed among pediatric athletes, determine preparticipation screening options and optimal symptom-driven evaluations in children, and consider best practices for pediatric athletes with several key cardiac conditions are detailed. The purpose of this document is to represent the first primary reference available to providers who care for pediatric athletes with cardiovascular concerns.

Nbeal2 Knockout Mice Are Not Protected Against Hypoxia-Induced Pulmonary Vascular Remodeling And Pulmonary Hypertension, Janelle N Posey, Mariah Jordan, Caitlin V Lewis, Christina Sul, Evgenia Dobrinskikh, Delaney Swindle, Frederik Denorme, David Irwin, Jorge Di Paola, Kurt Stenmark, Eva S Nozik, Cassidy Delaney

2020-Current year OA Pubs

Inflammation drives the initiation and progression of pulmonary hypertension (PH). Platelets, increasingly recognized as immune cells, are activated and increased in the lungs of patients with PH. Platelet activation leads to the release of α-granule chemokines, many of which are implicated in PH. We hypothesized that hypoxia-induced secretion of platelet α-granule-stored proteins and PH would be prevented in Neurobeachin-like 2 knockout (Nbeal2-/-) α-granule-deficient mice. Wild-type (WT) and Nbeal2-/- mice were maintained in normoxia or exposed to 10% hypobaric hypoxia for 3, 14, 21, or 35 days. We observed macrothrombocytopenia, increased circulating neutrophils and monocytes, and increased lung interstitial macrophages (IMs) …

Gpat4 Sustains Endoplasmic Reticulum Homeostasis In Endocardial Cells And Safeguards Heart Development, Youjun Wang, Zhongzhou Yang

Faculty, Staff and Student Publications

The endocardium plays a pivotal role in governing myocardial development, and understanding the intrinsic regulatory insights will help apprehend pathological cardiomyopathy. Glycerol-3-phosphate acyltransferase 4 (GPAT4) is an endoplasmic reticulum (ER) membrane anchored protein. While the role of GPAT4 in glycerophospholipid biosynthesis is well established, its function in the ER is less explored. Here, we generate Gpat4 global and tissue-specific knockout mice and identify the essential role of GPAT4 in endocardial development. Deficiency of GPAT4 provokes endocardial ER stress response and enhances ER-mitochondrial (ER-mito) communications, leading to mitochondrial DNA (mtDNA) escape. As a result, the cGAS-STING pathway is triggered to stimulate …

Goat Tying Styles Impact On Performance Consistency With Rodeo Competitors In The National Intercollegiate Rodeo Association Ozark Region, Marie Baxley, C.A. Shea Porr, Thomas Powell

Honors College Theses

Goat tying is a rodeo event involving dismounting a horse, and flanking and tying three legs of a goat. Flanking is defined as picking a goat up and setting it on the ground on its side. Flank/gather (FG) is a style where riders scoop the legs with the right hand and then place them in the left. Catch the flank (CF), stuffing (ST), and funneling (FN) are other methods that involve the goats’ legs landing together so the right hand is not needed for gathering. The objectives of this study were to determine 1) if flanking method affects performance, and …

Daily Acute Intermittent Hypoxia Elicits Age & Sex-Dependent Changes In Molecules Regulating Phrenic Motor Plasticity, Jayakrishnan Nair, Alexandria Marciante, Carter Lurk, Mia Kelly, Maclain Capron, Gordon Mitchell

Department of Physical Therapy Faculty Papers

Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Exposure to repetitive daily AIH (dAIH) enhances pLTF, a form of metaplasticity. Little is known concerning cellular mechanisms giving rise to dAIH-induced metaplasticity and the age-dependent sexual dimorphism of AIH associated pro-plasticity mRNA expression. To test if age, sex, and dAIH effects are associated with differential expression of molecules that regulate the Q- and S-pathways and their cross-talk interactions to phrenic motor facilitation, we analyzed key regulatory molecules in ventral spinal (C3-C5) homogenates from young (3-month) and middle-aged (12-month) male and female Sprague-Dawley …

Achieving Periodontal Disease Stabilization: Assessing The Impact Of Laser Therapy In Scaling And Root Planing And Periodontal Maintenance Visits, Cassandra Charlotte Cooper

Dental Hygiene ETDs

Purpose: This study examined the effectiveness of laser utilization in stabilizing periodontal disease over a one-year period. This research focused on the results following scaling and root planing with adjunctive laser-assisted periodontal therapy and laser bacterial reduction at subsequent periodontal maintenance visits. While short-term advantages are documented in the literature, research on sustained effectiveness is limited. Methods: A retrospective chart review of 30 adult patients who received the above treatment was conducted. Periodontal charting was recorded at three visits over one year. Data was collected and analyzed utilizing Statistical Package for Social Sciences (SPSS) to determine statistical significance of periodontal …

Vestibular Neurons Link Motion Sickness, Behavioural Thermoregulation And Metabolic Balance In Mice, Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C Bean, Kristine M Conde, Mengjie Wang, Yongxiang Li, Olivia Z Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Motion sickness is associated with thermoregulation and metabolic control, but the underlying neural circuitry remains largely unknown. Here we show that neurons in the medial vestibular nuclei parvocellular part (MVePC) mediate the hypothermic responses induced by motion. Reactivation of motion-sensitive MVePC neurons recapitulates motion sickness in mice. We show that motion-activated neurons in the MVePC are glutamatergic (MVePCGlu), and that optogenetic stimulation of MVePCGlu neurons mimics motion-induced hypothermia by signalling to the lateral parabrachial nucleus (LPBN). Acute inhibition of MVePC-LPBN circuitry abrogates motion-induced hypothermia. Finally, we show that chronic inhibition of MVePCGlu neurons prevents diet-induced obesity and improves glucose homeostasis …

The Impact Of Perceived Discrimination On Mental And Physical Health Among The Hispanic Immigrant Population, Cheyla Tabares Cuesta

Undergraduate Theses

Discrimination has profoundly shaped the lives of individuals within disadvantaged communities, but its impact on mental and physical health has often been overlooked. In this project, I review literature on perceived discrimination based on immigrant status and its effects on psychological and physical health and examine a potential mediator and moderator of these relationships. Specifically, the relationships between immigration-based discrimination and both mental health and physical health may be mediated by perceived stress, meaning that discrimination may lead to higher stress levels, which results in poorer health outcomes. Furthermore, these relationships may be moderated by psychological resilience; individuals with higher …

Alterations In Dna Methylation, Proteomic, And Metabolomic Profiles In African Ancestry Populations With Apol1 Risk Alleles, Yishu Qu, Mariaelisa Graff, Julian Avila, Eric Boerwinkle, Steven Buyske, Clary B Clish, Dan Cruz, Myriam Fornage, Robert E Gerzsten, Christopher R Gignoux, Lashaunta Glover, Lifang Hou, Anne E Justice, Charles Kooperberg, Holly Kramer, Leslie Lange, Ruth J F Loos, Tara Matise, Opeyemi A Olabisi, Ulrike Peters, Laura M Raffield, Alex P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Bing Yu, Yinan Zheng, Kari E North, Amy K Mottl, Heather M Highland, Maggie A Stanislawski

Faculty, Staff and Student Publications

Key Points:

1. We aimed to elucidate potential methylation, proteomic, and metabolomic mechanisms by which APOL1 variants may be linked to kidney disease.

2. We report distinct methylation profiling between APOL1 risk allele carriers and noncarriers, many near APOL gene family.

3. We report higher APOL1 protein and lower C18:1 cholesteryl ester in two risk allele carriers.

Background: The APOL1 high-risk haplotype has been associated with CKD and the deterioration of kidney function, particularly in populations with West African ancestry. However, the mechanisms by which APOL1 risk variants increase the risk for kidney disease and its progression have not been fully elucidated.

Methods: …

Mechanistic Insights Into The Structure-Based Design Of A Cspz-Targeting Lyme Disease Vaccine, Alan Wang, Yi-Lin Chen, Jungsoon Lee, Zhuyun Liu, Xiuli Yang, Ulrich Strych, Dagnija Tupina, Inara Akopjana, Maria-Elena Bottazzi, Utpal Pal, Ching-Lin Hsieh, Wen-Hsiang Chen, Yi-Pin Lin

Faculty, Staff and Students Publications

Borrelia burgdorferi (Bb) causes Lyme disease (LD), one of the most common vector-borne diseases in the Northern Hemisphere. Here, we solve the crystal structure of a mutated Bb vaccine antigen, CspZ-YA that lacks the ability to bind to host complement factor H (FH). We generate point mutants of CspZ-YA and identify CspZ-YAI183Y and CspZ-YAC187S to trigger more robust bactericidal responses. Compared to CspZ-YA, these CspZ-YA mutants require a lower immunization frequency to protect mice from LD-associated inflammation and bacterial colonization. Antigenicity of wild-type and mutant CspZ-YA proteins are similar, as measured using sera from infected people or immunized …

Shared Pathway Of Wdfy4-Dependent Cross-Presentation Of Immune Complexes By Cdc1 And Cdc2, Suin Jo, Ray A Ohara, Derek J Theisen, Sunkyung Kim, Tiantian Liu, Christopher B Bullock, Michelle He, Feiya Ou, Jing Chen, Sytse J Piersma, J Luke Postoak, Wayne M Yokoyama, Michael S Diamond, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to …